covid: 3rd vaccine dose for immunocompromised

 A French study documented an improved immunologic response after a third dose of the Pfizer vaccine in immunocompromised patients (see covid immunocomp getting 3rd dose nejm2021 in dropbox or DOI: 10.1056/NEJMc2108861) 

 

Details: 

-- 101 consecutive solid organ transplant recipients were given a third dose of the Pfizer vaccine 

-- mean age 58, 62% men, in a retrospective study 

-- transplant recipients: 78 kidney, 12 liver, 8 lung or heart, and 3 pancreas  

-- time from transplant to initiating vaccination was 98 months 

-- first two doses were given one month apart, third dose was 61 days after the second dose 

-- medications: glucocorticoids 87%, calcineurin inhibitors 79%, mycophenolic acid 63%, mammalian target of rapamycin inhibitors 30%, belatacept 12% 

-- antibody levels were assessed against the SARS-CoV-2 spike protein 

 

Results: 

-- prevalence of anti-SARS-CoV-2 antibodies: 

    -- prior to the first of vaccine: 0% (0-4%), 0 patients 

    -- prior to the second dose: 4% (1-10%), 4 patients 

    -- prior to the third dose: 40% (31-51%), 40 patients 

    -- four weeks after the third dose: 68% (58-77%), 67 patients 

-- 59 patients were seronegative before the third dose, 26 (44% of them) became seropositive at four weeks after the third dose 

-- all patients who were seropositive before the third dose were seropositive 4 weeks later: antibody titers increased from 36 to 2676 one month after the third dose, p<0.001 

-- those who did not develop an antibody titer were older, had a higher degree of immunosuppression, and a lower eGFR 

-- no cases of Covid developed in any patient after the third dose 

-- no serious adverse events were reported 

 

Commentary: 

-- the French National Authority for Health has recommended a third dose of vaccine in immunosuppressed patients after prior reports found severe cases of Covid in transplant recipients who had previously received the standard two doses of vaccine

-- there have been a few prior studies with similar findings to the above: 

   -- Johns Hopkins study: 21 days after the first mRNA vaccine, antibody was detected in 15% of 658 recipients who had had a solid organ transplant; 29 days after second dose: 54% had detectable antibodies; 46% had no detectable antibody after dose 1 or dose 2. Of the 473 on anti-metabolites, 35% had no antibody response after either dose (see Boyarsky BJ. JAMA 2021; 325: 2204-6) 

    -- a larger study of 895 patients in France with solid organ transplants also found a weak immunogenic response to mRNA vaccines (33.8% one month after the second dose), though there was a higher response in those getting liver transplants (see https://www.acpjournals.org/doi/10.7326/M21-1341 

    -- and clinical outcomes may be worse: a Mayo Clinics study found that 7 patients with solid organ transplants developed Covid-19 after vaccination, 5 of whom had 2 doses of the Pfizer vaccine and developed Covid after a median of 28 days after 2nd dose.  one patient did have antispike antibody at the time of Covid diagnosis, though low titer. all were hospitalized with severe Covid infections: see https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8251487/pdf/AJT-9999-0.pdf

-- I am unaware of any data on the safety or efficacy of Covid vaccines in those who are significantly immunocompromised outside of those with transplants. There is a recent Frequently Asked Question document from the HIV Medicine Association and the IDSA that was just released on 6/15/21, though it does not address this question for those immunocompromised from hiv: https://www.hivma.org/globalassets/covid-19-vaccines-hiv-faq.pdf 

-- the bigger question is what level of immunocompromise should people be either tested for antibody response or just get a 3rd vaccination: those with lupus (and what degree? lupus nephritis?), those on certain meds (steroids/how long and what dose, methotrexate, etc), those with poorly controlled diabetes (and at what level of A1c), those with HIV and CD4 <200 (or different target), those with renal failure (and what level? there are a couple of small studies i have seen on dialysis patients, with mixed antibody results from vaccination)

 

Limitations: 

--would be great to have more granular data. for example, is there some combination of specific organ transplant plus medications (if so, which ones?, combinations?)

--we still do not know how to interpret antibody titers: is there a threshold for protection, though would depend on which antibodies were measured (eg, hepatitis B has surface antibody threshold >10 to be clinically significant post-vaccination). do some people have non-detectable antibodies but memory cells/T-cells that are sufficient to fight off the virus?

    --to be sure, we really need data on clinical outcomes after 2 vs 3 shots, though the Mayo Clinics study above is suggestive that Covid infections may be an important clinical issue after solid organ transplant

So, not so surprisingly: one size does not quite fit all. Immunocompromised people may well need three doses to get an adequate response to mRNA vaccines, as opposed to immunocompetent people who typically mount impressive responses after a single-dose. It is important to know if non-transplant recipients who are immunocompromised, such as from poorly controlled diabetes or HIV or on steroids, would benefit from a third mRNA injection... 

geoff

 

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